Acta Pharmaceutica Sinica B | VOL. 12
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A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

Publication Date Aug 1, 2022

Abstract

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient invivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Concepts

Modified Messenger RNA IL-10 mRNA Delivery Of mRNA Designed Delivery System Ulcerative Colitis Treatment Strategy For Efficient Delivery Ulcerative Colitis Systemic Toxicity Acute Murine Models Delivery System

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